1. Field of the Invention
The present invention relates to a material for contact lenses which is suitable as a polymer having biocompatibility and oxygen permeability, and to soft contact lenses. The soft contact lenses of the present invention have the water content of, for example, from 15 to 35%, and excellent flexibility and oxygen permeability.
2. Related Art
Clinical results have indicated that a use of contact lenses reduces the supply of oxygen from the air, which may sometimes cause inhibiting proliferation of corneal epithelial cells and corneal swelling. Accordingly, an improvement of the material in oxygen permeability has been attempted so far in order to provide contact lenses having higher safety.
In the improvement in oxygen permeability of hard contact lenses, introduction of siloxanyl methacrylate, fluoroalkyl methacrylate or the like has been attempted. This method remarkably improved oxygen permeability of hard contact lenses; however, the aggravation of the feel in use caused by the hard material has not be improved at all. On the other hand, soft contact lenses are categorized into no-water-containing soft contact lenses and water-containing (hydrogel) lenses. As for the no-water-containing soft contact lenses, silicone lenses, for example, have high oxygen permeability; however, too much elasticity causes lenses to stick to the cornea, and accordingly, they have not been practically utilized. Lenses made of (meth)acrylic esters have a rather low oxygen permeability constant, which is an insufficient value. The water-containing soft contact lenses are known to be comfortable in use due to flexibility of the material; however, their oxygen permeability is derived from the water content of the lenses, and thereby lower compared with that of hard contact lenses. For example, a material for water-containing soft lenses having the water content of 80% has the oxygen permeability constant of about 40xc3x9710xe2x88x9211 (cm2/sec)xc2x7(mL O2/mLxc3x97mmHg).
A number of reports have been made with respect to the oxygen amount necessary for the cornea. Mishima compared the oxygen permeability of contact lenses with the corneal change in use, and reported that Dk/L of a contact lens corresponding to the cornea swelling ratio of 0 (the value obtained by dividing the Dk value (oxygen permeability) by the thickness of the lens (cm)) was not less than 70xc3x9710xe2x88x929 (Nichi-Kore-Shi 36: 1-12, 1994). The oxygen permeability of common soft contact lenses depends on the water content; accordingly, it is extremely difficult to prepare lenses satisfying the Dk/L value (oxygen transmissibility) of 70xc3x9710xe2x88x929.
Accordingly, various siloxane-containing polymers have been disclosed in order to improve oxygen permeability of soft contact lenses. For example, Japanese Patent Laid-Open No. 294818/1991 (hereinafter referred to as prior art 1) discloses, as a soft contact lense having excellent oxygen permeability, low water-containing soft contact lenses which substantially comprise an organosiloxanyl (meth)acrylate, a fluorine-containing monomer and dimethylacrylamide as the main components. In this case, oxygen permeability may be improved by introducing silicone and the fluorine-containing monomer as the components of the contact lenses; however, the improvement is insufficient, and the resulting lenses are hard and poor in shape restorablility, which is caused by low molecule movability between a moiety having silicone group or fluorine group and a functional group (e.g., methacroyl group).
International Patent Publication (KOHYO) No.502949/1991 (hereinafter referred to as prior art 2) discloses soft contact lenses having excellent oxygen permeability which comprise a siloxane macromer as the main component. In this case, soft contact lenses having high oxygen permeability and excellent flexibility can be obtained by using a siloxane macromer having a high molecular weight as the main component. However, the macromer having the structure disclosed in the prior art 2 has the siloxane structure in the main chain and functional groups at the both ends, and thereby, the both ends of the macromer bind to other components in the polymer to inhibit the movability of the siloxane structure. Therefore, it cannot be actually expected to dramatically improve the oxygen permeability.
Accordingly, an object of the present invention is to provide a material for contact lenses and soft contact lenses having excellent flexibility and oxygen permeability.
The inventors of the present invention made intensive studies on the basis of the aforementioned prior arts in order to develop soft contact lenses having oxygen permeability in the same degree as or more than hard contact lenses. As a result, they successfully developed a material for soft contact lenses having satisfactory flexibility and oxygen permeability by using a siloxane macromer in which a polymerizing group binds to the polysiloxane side chain by means of urethane bond to maintain high movability of the siloxane structure which contributes to oxygen permeability in the polymer. The present invention was achieved on the basis of these findings.
The present invention relates to a material for contact lenses which comprises a copolymer essentially comprising a siloxane macromer of component (A) which has the number-average molecular weight of from about 1,000 to 10,000 and is represented by the general formula (I): 
wherein R1, R2 and R3 are independently selected from C1-C4 alkyl groups; R4 is selected from C1-C6 alkyl groups; R5 is a residue obtained by removing NCO group from an aliphatic, alicyclic or aromatic diisocyanate; R6, R7, R8 and R9 are independently selected from C1-C3 alkylene groups; n is an integer of from 4 to 80; and m and p are independently an integer of from 3 to 40,
a water-insoluble monoolefin monomer of component (B), and a water-soluble monoolefin monomer of component (C).
The present invention further relates to a soft contact lens which is obtained by molding the aforementioned material for contact lenses in the shape of contact lens, and making the lens contain water.
In addition, the present invention relates to a soft contact lens which is obtained by injecting to a mold in the shape of contact lens a monomer mixture comprising a siloxane macromer of component (A) which has the number-average molecular weight of from about 1,000 to 10,000 and is represented by the general formula (I): 
wherein R1, R2 and R3 are independently selected from C1-C4 alkyl groups; R4 is selected from C1-C6 alkyl groups; R5 is a residue obtained by removing NCO group from an aliphatic, alicyclic or aromatic diisocyanate; R6, R7, R8 and R9 are independently selected from C1-C3 alkylene groups; n is an integer of from 4 to 80; and m and p are independently an integer of from 3 to 40,
a water-insoluble monoolefin monomer of component (B), and a water-soluble monoolefin monomer of component (C); copolymerizing the monomer mixture; and making the resulting copolymer contain water.
The material for contact lenses of the present invention comprises a copolymer essentially comprising a siloxane macromer of component (A), a water-insoluble monoolefin monomer of component (B), and a water-soluble monoolefin monomer of component (C).
The siloxane macromer of component (A) is a component which may provide excellent flexibility and oxygen permeability, and the water-insoluble monoolefin monomer of component (B) and the water-soluble monoolefin monomer of component (C) are those which may provide properties corresponding to the purposes such as flexibility, oxygen permeability, and the desired water content. The material for contact lenses of the present invention comprises the copolymer components comprising these 3 components, thereby is a material for contact lenses having excellent flexibility and oxygen permeability, which have not been obtained in the conventional materials.
The siloxane macromer of component (A) is represented by the aforementioned general formula (I) and has the number-average molecular weight of from about 1,000 to 10,000. When the number-average molecular weight of the siloxane macromer of component (A) is less than about 1,000, the lens cannot have sufficient oxygen permeability, and when it is more than about 10,000, the molecular weight is so high that the compatibility with other copolymer components may be degraded, and the component (A) may sometimes dissolve insufficiently in formulation. The number-average molecular weight of the siloxane macromer of component (A) is preferably from 2,000 to 8,000.
In the aforementioned general formula (I) which represents the siloxane macromer of component (A), R1, R2 and R3 may be the same or different. The C1-C4 alkyl groups include, for example, methyl group, ethyl group, propyl group, n-butyl group, tert-butyl group and the like, and preferred is methyl group. The C1-C6 alkyl groups represented by R4 include, for example, methyl group, ethyl group, propyl group, n-butyl group, n-pentyl group, n-hexyl group and the like, and preferred is n-butyl group. In the residue obtained by removing NCO group from an aliphatic, alicyclic or aromatic diisocyanate represented by R5, the aliphatic diisocyanate includes, for example, 1,4-diisocyanatobutane, 1,6-diisocyanatohexane and the like. The alicyclic diisocyanate includes, for example, 1,2-diisocyanatocyclohexane, 1,3-diisocyanatocyclohexane, isophorone diisocyanate and the like. The aromatic diisocyanate includes, for example, 2,4-toluenediisocyanate, 2,6-toluenediisocyanate, diphenylmethane-4,4xe2x80x2-diisocyanate and the like. The residue obtained by removing NCO group from an aliphatic, alicyclic or aromatic diisocyanate represented by R5 preferably has the isophorone structure. R6, R7, R8 and R9 may be the same or different. The C1-C3 alkylene groups include, for example, methylene group, ethylene group, propylene group and the like, and preferred is C2 alkylene (ethylene) group.
The symbol xe2x80x9cnxe2x80x9d is an integer of from 4 to 80. It is not preferred that xe2x80x9cnxe2x80x9d is less than 4 because the lens cannot have sufficient oxygen permeability, and that xe2x80x9cnxe2x80x9d is more than 80 because the compatibility with other copolymer components may be degraded and the component (A) may sometimes dissolve insufficiently in formulation. The symbol xe2x80x9cnxe2x80x9d is preferably an integer of from 4 to 60, and more preferably an integer of from 4 to 40. The symbols xe2x80x9cmxe2x80x9d and xe2x80x9cpxe2x80x9d may be the same or different, and are integers of from 3 to 40. It is not preferred that xe2x80x9cmxe2x80x9d and xe2x80x9cpxe2x80x9d are less than 3 because the lens cannot have sufficient flexibility, and that they are more than 40 because the lens tends to have reduced strength or to be fragile. The symbols xe2x80x9cmxe2x80x9d and xe2x80x9cpxe2x80x9d are preferably integers of from 3 to 30, and more preferably integers of from 3 to 20.
The material for contact lenses of the present invention is preferably those wherein R1, R2 and R3 are methyl groups, R4 is n-butyl group, xe2x80x9cnxe2x80x9d is an integer of from 4 to 60, and xe2x80x9cmxe2x80x9d and xe2x80x9cpxe2x80x9d are independently an integer of from 3 to 30 in the general formula (I) because they have good physical properties such as flexibility and oxygen permeability.
The siloxane macromer of component (A) is preferably a component represented by the general formula (II): 
In the formula, R10 is a residue obtained by removing NCO group from an aliphatic, alicyclic or aromatic diisocyanate. The aliphatic diisocyanate includes, for example, 1,4-diisocyanatobutane, 1,6-diisocyanatohexane and the like. The alicyclic diisocyanate includes, for example, 1,2-diisocyanatocyclohexane, 1,3-diisocyanatocyclohexane, isophorone diisocyanate and the like. The aromatic diisocyanate includes, for example, 2,4-toluenediisocyanate, 2,6-toluenediisocyanate, diphenylmethane-4,4xe2x80x2-diisocyanate and the like. The residue obtained by removing NCO group from an aliphatic, alicyclic or aromatic diisocyanate represented by R10 preferably has the isophorone structure.
The symbol xe2x80x9cnxe2x80x2xe2x80x9d is an integer of from 4 to 40. When xe2x80x9cnxe2x80x2xe2x80x9d is in this range, the lens may advantageously have much better physical properties such as the strength, flexibility, and oxygen permeability. The symbol xe2x80x9cnxe2x80x2xe2x80x9d is preferably an integer of from 4 to 30. The symbols xe2x80x9cmxe2x80x2xe2x80x9d and xe2x80x9cpxe2x80x2xe2x80x9d are the same or different, and are integers of from 3 to 20. The symbols xe2x80x9cmxe2x80x2xe2x80x9d and xe2x80x9cpxe2x80x2xe2x80x9d to be in the range of from 3 to 20 provide advantages of much better physical properties such as the strength, flexibility and oxygen permeability of the lens. The symbols xe2x80x9cmxe2x80x2xe2x80x9d and xe2x80x9cpxe2x80x2xe2x80x9d are preferably integers of from 3 to 15.
The water-insoluble monoolefin monomer of component (B) is used for the purpose of providing oxygen permeability to the material for contact lenses as an assistance, and improving the mechanical strength. The water-insoluble monoolefin monomer of component (B) includes, for example, components derived from one or more monomers selected from the group consisting of tris (trimethylsiloxy)-xcex3-methacryloxypropylsilane, 2,2,2-trifluoroethyl methacrylate, hexafluoroisopropyl methacrylate, and perfluorooctylethyloxypropylene methacrylate.
The water-soluble monoolefin monomer of component (C) is used for the purpose of adjusting the water content of the soft contact lenses prepared from the material for contact lenses, and providing flexibility as an assistance. The water-soluble monoolefin monomer of component (C) includes, for example, components derived from at least one or more monomers selected from the group consisting of 2-hydroxyethyl methacrylate, N,N-dimethylacrylamide, N-vinyl-2-pyrrolidone, and methacrylic acid.
In the material for contact lenses of the present invention, the content of the siloxane macromer of component (A) is preferably from 10 to 60% by weight. The content of the siloxane macromer of component (A) of 10% by weight or more can provide sufficient flexibility and oxygen permeability to the lenses prepared from the material, and that of 60% by weight or less can prevent the bridge density from excessively increasing and the lenses from being brittle. More preferably, the content of the siloxane macromer of component (A) is from 15 to 50% by weight.
In the material for contact lenses of the present invention, the content of the water-insoluble monoolefin monomer of component (B) is preferably from 10 to 50% by weight. The content of the water-insoluble monoolefin monomer of component (B) of 10% by weight or more can provide a sufficient effect of addition of the water-insoluble monoolefin monomer of component (B), and that of 50% by weight or less can provide adequate flexibility and shape recovery to the lenses. More preferably, the content of the water-insoluble monoolefin monomer of component (B) is from 15 to 45% by weight.
In the material for contact lenses of the present invention, the content of the water-soluble monoolefin monomer of component (C) is preferably from 10 to 45% by weight. The content of the water-soluble monoolefin monomer of component (C) of 10% by weight or more can provide an appropriate water content to the lenses prepared from the material, and that of 45% by weight or less can prevent the water content in the lenses prepared from the material from excessively increasing, and oxygen permeability, which depends upon the water content, from markedly decreasing. More preferably, the content of the water-soluble monoolefin monomer of component (C) is from 15 to 40% by weight.
The material for contact lenses of the present invention may be a copolymer which comprises, in addition to the aforementioned 3 components, a component derived from a bridging monomer, for example, ethylene glycol di(meth)acrylate, diethylene glycol di(meth)acrylate, triethylene glycol di(meth)acrylate, allyl methacrylate, diallyl phthalate, diallyl maleate, diallyl isophthalate, triallyl isocyanurate and the like, in order to obtain the mechanical strength and endurance. In the present specification, xe2x80x9c(meth)acrylatexe2x80x9d means both of acrylate and methacrylate. The content of the aforementioned bridging monomer is preferably from 0.01 to 1% by weight to the total amount of the copolymerizing components. The amount of the bridging monomer of 0.01% by weight or more can provide the effect of addition of the mechanical strength and endurance, and that of 1% by weight or less can prevent the resulting soft contact lenses from being brittle.
The material for contact lenses of the present invention may further contain, for example, a polymerizing ultraviolet absorber, a polymerizing coloring matter and the like as copolymerizing components in order to add ultraviolet absorbability or a color to the resulting soft contact lenses. Specific examples of the aforementioned polymerizing ultraviolet absorber include 5-chloro-2-[2-hydroxy-5-(xcex2-methacryloyloxyethylcarbamoylox yethyl)]phenyl-2H-benzotriazole, 2-[2-hydroxy-5-(xcex2-methacryloyloxyethylcarbamoyloxyethyl)]p henyl-2H-benzotriazole, 5-chloro-2-[2-hydroxy-4-(p-vinylbenzyloxy-2-hydroxypropylo xy)]phenyl-2H-benzotriazole and the like.
Specific examples of the aforementioned polymerizing coloring matter include 1,4-bis(4-vinylbenzylamino)anthraquinone, 1-p-hydroxybenzylamino-4-p-vinylbenzylaminoanthraquinone, 1-anilino-4-methacryloylaminoanthraquinone and the like.
When coloring the contact lenses made of the material of the present invention, the vat dyeing method may be used which comprises soaking the lenses in a vat without using these coloring matters to sufficiently impregnate the whole lenses with a leucocompound of a dye, and then soaking the lenses in an oxidizing bath to convert the leucocompound into an oxidative compound and fix the dye. As other coloring agents, the material for contact lenses of the present invention may contain a phthalocyanine coloring matter such as Alcian Blue 8GX and Alcian Green 2GX. The suitable content of the aforementioned polymerizing ultraviolet absorber and polymerizing dye is 5% by weight or less of the copolymerizing components, and the particularly preferred is from 0.02 to 3% by weight, owing to the effect of the thickness of the lens prepared from the material. The amount of 5% by weight or less can prevent a decrease in the mechanical strength of the resulting contact lenses, and is preferable in safety as contact lenses which directly contact to the living body.
The present invention includes a soft contact lens which is obtained by molding the material for contact lenses according to the aforementioned present invention in the shape of contact lens, and making the lens contain water. The method of molding the material for contact lenses in the shape of contact lens and making the lens contain water may be performed in a conventional manner.
The present invention further includes a soft contact lens which is obtained by injecting to a mold in the shape of contact lens a monomer mixture comprising a siloxane macromer of component (A), a water-insoluble monoolefin monomer of component (B), and a water-soluble monoolefin monomer of component (C); copolymerizing the monomer mixture; and making the resulting copolymer contain water.
The siloxane macromer of component (A), the water-insoluble monoolefin monomer of component (B), and the water-soluble monoolefin monomer of component (C) are the same as those explained for the aforementioned material for contact lenses.
Among the soft contact lenses of the present invention, preferred are those wherein R1, R2 and R3 are methyl groups, R4 is n-butyl group, xe2x80x9cnxe2x80x9d is an integer of from 4 to 60, and xe2x80x9cmxe2x80x9d and xe2x80x9cpxe2x80x9d are independently an integer of from 3 to 30 in the aforementioned general formula (I) from the viewpoint of good physical properties such as the strength, flexibility, and oxygen permeability of the lenses.
In the soft contact lenses of the present invention, the siloxane macromer (A) is preferably a monomer represented by the general formula (II) which is explained for the aforementioned material for contact lenses from the viewpoint of much better physical properties such as the strength, flexibility and oxygen permeability of the lenses.
For the preparation of the material for contact lenses and the soft contact lenses of the present invention, a mixture containing the aforementioned monomer is at first added with a polymerization initiator and sufficiently stirred to give a homogeneous monomer mixture. The suitable content of the siloxane macromer (A) in the monomer mixture is from 10 to 60% by weight, that of the water-insoluble monoolefin monomer (B) is from 10 to 50% by weight, and that of the water-soluble monoolefin monomer (C) is from 10 to 45% by weight. As the polymerization initiator used herein, a peroxide such as lauroyl peroxide, qumene hydroperoxide, and benzoyl peroxide, 2,2xe2x80x2-azobis(2,4-dimethylvaleronitrile), and 2,2xe2x80x2-azobisisobutyronitrile may be used, and when applying the photopolymerization, a photoinitiator such as benzoin methyl ether, 1-hydroxycyclohexyl phenyl ketone, 2,2-dimethoxy-2-phenylacetophenone, and 2-hydroxy-2-dimethoxy-1-phenylpropane-1-one may be used.
In addition, the polymerization may be performed in the presence or absence of an appropriate diluent. The appropriate diluent may be any one so long as it homogeneously dissolves the monomer components used. The diluent includes, for example, an alcohol (e.g., ethanol, isopropanol, n-hexanol), a dipolar aprotic solvent such as dimethylsulfoxide, an ether (e.g., THF, dimethoxyethane), an ester (e.g., propyl acetate, isopropyl acetate, isobutyl acetate, tert-butyl acetate, butyl propionate, butyl butyrate), a mixed solvent of water and an alcohol (a water/ethanol mixed solvent) and the like. When using a diluent, the effects may be sometimes expected which are an easy injection into a mold caused by a decrease in the viscosity of the monomer mixture, and an improvement of the mechanical strength of the resulting lens by effective removal of the polymerization heat in polymerization.
The aforementioned monomer mixture is injected to a mold for preparation of contact lenses with or without the shape of contact lens, and then polymerized. The mold is in the combined shape having a convex curvature and a concave curvature, and may be made of a material such as metal, glass, resin and the like. The material preferably has excellent removability of the polymer and excellent resistance to solvent and heat. Among such materials, a mold made of resin is preferred because it can easily be prepared in the shape necessary to the desired lens design. The resin material is preferably selected from those having low contraction in formation, good surface transcription from the die, and excellent dimensional accuracy and resistance to solvent. Such resin materials include, for example, polyethylene, polypropylene, polymethylpentene (TPX), polysulfone, polyphenylene sulfide, cyclic olefin copolymers (e.g., xe2x80x9cApelxe2x80x9d, Mitsui Petrochemical Co. Ltd.; xe2x80x9cZEONEXxe2x80x9d, Nippon Zeon Co. Ltd.) and the like. When injecting the monomer, the mold is sufficiently exposed to reduced pressure to remove the substance affecting the reaction such as water and oxygen which exists on the surface of the mold, then the mold is purged with an inert gas such as nitrogen and argon, and then the monomer mixture is injected to the mold. Injection of the monomer mixture is preferably performed under an atmosphere of an inert gas such as nitrogen and argon.
The polymerization method includes, for example, a method of elevating the temperature stepwise or continuously in the range of from 25 to 120xc2x0 C., and completing the polymerization for 1 to 24 hours. In this method, it is desirable that the polymerization is carried out under an atmosphere of an inert gas such as nitrogen and argon in the polymerization furnace at atmospheric pressure or under pressurized conditions. In the polymerization, a photopolymerization method by ultraviolet, visible radiation or the like may be applied after adding the aforementioned photopolymerization initiator.
After the polymerization, the lens is taken out of the mold, and then it may be applied to a known surface treatment if necessary. In the surface treatment with plasma, for example, the technique and apparatus known so far may be used, and an active gas such as air, oxygen, hydrogen and nitrogen, or an inert gas such as helium, neon and argon, and an organic low-molecular compound such as N-vinylpyrrolidone and acetylene may be used.
Molding Methods for the Shape of Contact Lens
When molding the copolymer as contact lenses, a molding method commonly used by persons with ordinary skill in the art may be applied. Such a molding method includes, for example, a cutting method, and a method of cutting or freeze-cutting the copolymer may be carried out after obtaining the copolymer in the shape of bars or blocks to mold the copolymer into the shape of contact lens.
Water-Imparting Treatment Methods
The mold in the shape of contact lens obtained by cutting or the Like, or the copolymer taken out of the mold in the shape of contact lens for preparation of contact lenses may be soaked in physiological saline or a preserving medium for soft contact lenses to be impregnated with water, and the desired contact lenses can be obtained.
In the soft contact lenses of the present invention, the water content and the oxygen permeability constant can be adjusted to the range of from 15 to 35% and not less than 7xc3x9710xe2x88x9211 (cm2/sec)xc2x7(mL O2/mLxc3x97mmHg), respectively, by means of adjusting the aforementioned monomer components and the ratio thereof.